Skip to content
2000
image of Design, Synthesis, In Vitro and In Silico Biological Evaluation of Novel Benzimidazole Derivatives as Antibacterial and Antifungal Agents

Abstract

Background

Drug-resistant microorganisms are a major concern, particularly as more strains develop resistance to various antimicrobial agents. Some microbes are currently immune to all antibiotics. Consequently, it is imperative to develop novel drugs that maintain their effectiveness. The benzimidazole nucleus can be found in a wide variety of heterocyclic compounds in nature. Numerous investigations have been conducted on the physiological effects of molecules containing this moiety.

Methods

Some more recent benzimidazole analogues were synthesized through the synthetic stages of o-phenylene diamine with 6-bromo-3,4-dihydro-2-chroman-2-carboxylic acid, followed by various electrophiles, in the search for new antibacterial and antifungal compounds with improved efficacy. 1H NMR, IR, and mass spectral data were used to determine the structures of these recently synthesized compounds. For their antibacterial and antifungal activities, all the produced compounds were tested. Besides their biological activities, these newly synthesized compounds were also docked into the active pocket of Dihydrofolate Reductase and Sterol 14-alpha demethylase to predict their binding modes concerning antibacterial and antifungal activities, respectively. Moreover, these predictions would be utilized for the exploration of the mechanism of action on selected enzyme subunits.

Results

Synthesis of 2-(6-bromochroman-2-yl)-1-benzo[]imidazole (4a-4y) derivatives was done using the classical Philipins condition. Spectral analysis revealed their structures. Amongst the synthesized scaffolds (4a-4y), target compounds and were active when compared with ciprofloxacin. Compound was found to be highly active compared to clotrimazole. Ligands 4w and 4e exhibited better binding energy on Dihydro Folate Reductase and Sterol 14-alpha demethylase (-7.1899 kcal/mol and -8.72613 kcal/mol) enzymes, respectively.

Conclusion

The current investigation may have shown that the produced compounds differ from one another, regardless of their structure or observable biological activity. In the quest for a new group of antibacterial and antifungal molecules, these compounds may be useful to society.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/cocat/10.2174/0122133372361592250709095118
2025-07-17
2025-09-08

  • From This Site

    /content/journals/cocat/10.2174/0122133372361592250709095118
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. O’Neil M.J. Smith M. Heckelman P.E. Eds.;The Merck Index. London, UK Royal Society of Chemistry 2001 213
    [Google Scholar]
  2. Wright J.B. The chemistry of the benzimidazoles. Chem. Rev. 1951 48 3 397 541 10.1021/cr60151a002 24541208
    [Google Scholar]
  3. Köhler P. The biochemical basis of anthelmintic action and resistance. Int. J. Parasitol. 2001 31 4 336 345 10.1016/S0020‑7519(01)00131‑X 11400692
    [Google Scholar]
  4. Preston P.N. Synthesis, reactions, and spectroscopic properties of benzimidazoles. Chem. Rev. 1974 74 3 279 314 10.1021/cr60289a001
    [Google Scholar]
  5. Breslin H.J. Miskowski T.A. Kukla M.J. De Winter H.L. Somers M.V.F. Roevens P.W.M. Kavash R.W. Tripeptidyl-peptidase II (TPP II) inhibitory activity of (S)-2,3-dihydro-2-(1 H -imidazol-2-yl)-1 H -indoles, a systematic SAR evaluation. Part 2. Bioorg. Med. Chem. Lett. 2003 13 24 4467 4471 10.1016/j.bmcl.2003.09.014 14643348
    [Google Scholar]
  6. Siva Kumar B.V. Vaidya S.D. Synthesis and anti-bacterial activity of some novel 2-(6-fluorochroman-2-yl)-1-alkyl/acyl/aroyl-1H-benzimidazoles. Eur. J. Med. Chem. 2006 41 599 604 10.1016/j.ejmech.2006.01.006 16527375
    [Google Scholar]
  7. Sharma S. Gupta M. Gupta M. Sahu J.K. Impact of benzimidazole containing scaffolds as anticancer agents through diverse modes of action. Curr. Bioact. Compd. 2023 19 9 e060423215472 10.2174/1573407219666230406082148
    [Google Scholar]
  8. Vaidya S.D. Siva Kumar B.V. Vinod Kumar R. Bhirud S.B. Mashelkar U.C. Synthesis, anti-bacterial, anti-asthmatic and anti-diabetic activities of novel N-substituted-2-(benzo[d]isoxazol-3-ylmethyl)-1H-benzimidazoles. Indian J. Heterocycl. Chem. 2005 14 197 200
    [Google Scholar]
  9. Kumar R.V. Gopal K.R. Kumar K.V.S.R.S. Facile synthesis and antimicrobial properties of 2-(substituted-benzylsulfanyl)-1h-benzimidazoles. J. Heterocycl. Chem. 2005 42 7 1405 1408 10.1002/jhet.5570420722
    [Google Scholar]
  10. Alimonti P. Castro G.L.N. Gupta M. Sahu J.K. The current landscape of immune checkpoint inhibitor immunotherapy for primary and metastatic brain tumors. Antibodies (Basel) 2023 12 2 27 44 10.3390/antib12020027 37092448
    [Google Scholar]
  11. Eaton P.E. Carlson G.R. Lee J.T. Phosphorus pentoxide-methanesulfonic acid convenient alternative to polyphosphoric acid. J. Org. Chem. 1973 38 23 4071 4073 10.1021/jo00987a028
    [Google Scholar]
  12. Kauffman J.M. Khalaj A. Litak P.T. Novinski J.A. Bajwa G.S. Synthesis and photophysical properties of fluorescent 2‐aryl‐1,3‐dialkylbenzimidazolium ions and a l‐alkyl‐2‐arylbenzimidazole with excited state intramolecular proton‐transfer. J. Heterocycl. Chem. 1994 31 4 957 965 10.1002/jhet.5570310444
    [Google Scholar]
  13. Krstulović L. Rastija V. de Carvalho L.P. Design, synthesis, antitumor, and antiplasmodial evaluation of new 7-chloroquinoline–benzimidazole hybrids. Molecules 2024 29 13 2997 10.3390/molecules29132997 38998949
    [Google Scholar]
  14. Gabriel C. Gabriel S. Grant E.H. Halstead B.S.J. Mingos D.M.P. Dielectric parameters relevant to microwave dielectric heating. Chem. Soc. Rev. 1998 27 213 224 10.1039/a827213z
    [Google Scholar]
  15. Elderfield R.C. Meyer V.B. The reaction of 1-methyl-2-(t-butyl)-benzimidazole with organolithium compounds. J. Am. Chem. Soc. 1954 76 7 1891 1893 10.1021/ja01636a046
    [Google Scholar]
  16. Selvi S.T. Nadaraj V. Mohan S. Sasi R. Hema M. Solvent free microwave synthesis and evaluation of antimicrobial activity of pyrimido[4,5-b]- and pyrazolo[3,4-b]quinolines. Bioorg. Med. Chem. 2006 14 11 3896 3903 10.1016/j.bmc.2006.01.048 16464602
    [Google Scholar]
  17. Minu M. Thangadurai A. Wakode S.R. Agrawal S.S. Narasimhan B. 3,4-disubstituted-1,2,3,4,5,6,7,8-octahydroquinazoline-2-thiones: synthesis, antimicrobial evaluation and QSAR investigations using hansch analysis. Arch. Pharm. (Weinheim) 2008 341 4 231 239 10.1002/ardp.200700153 18293436
    [Google Scholar]
  18. Kus C. Sözüdönmez F. Altanlar N. Synthesis and antimicrobial activity of some novel 2-[4-(substituted piperazin-/piperidin-1-ylcarbonyl)phenyl]-1H-benzimidazole derivatives. Arch. Pharm. (Weinheim) 2009 342 1 54 60 10.1002/ardp.200800084 19051196
    [Google Scholar]
  19. Gangadharappa B.S. Sharath R. Revanasiddappa P.D. Chandramohan V. Balasubramaniam M. Vardhineni T.P. Structural insights of metallo-beta-lactamase revealed an effective way of inhibition of enzyme by natural inhibitors. J. Biomol. Struct. Dyn. 2020 38 13 3757 3771 10.1080/07391102.2019.1667265 31514687
    [Google Scholar]
  20. Patel G.B. Mahire R.R. More D.H. Synthesis and characterization of benzimidazole derivatives by sonogashira coupling and evaluation of anthelmintic activity. Der. Pharma. Chemica. 2013 5 6 369 376
    [Google Scholar]
  21. Leela G.C. Priyanka N.C. Tanshinone IIA from Salvia miltiorrhiza alleviates follicular maturation arrest symptoms in zebrafish via binding to the human androgen receptors and modulating Tox3 and Dennd1a. Tissue Cell 2024 88 102404 10.1016/j.tice.2024.102404
    [Google Scholar]
  22. Dangi N. Mehendiratta H. Sharma S. In vitro antimicrobial activity of extracts from Kydia calycina and in-silico molecular docking studies of some phytochemicals. Chem. Lett. 2023 12 3 659 666 10.5267/j.ccl.2023.1.005
    [Google Scholar]
  23. Kumari R. Kumar R. Lynn A. g_mmpbsa--a GROMACS tool for high-throughput MM-PBSA calculations. J. Chem. Inf. Model. 2014 54 7 1951 1962 10.1021/ci500020m 24850022
    [Google Scholar]
  24. Gaikwad S. Ková Iková L. Pawar P. Gaikwad M. Bohá A. Dawane B. An update: Oxidative aromatization of TH?C to β-carbolines and their application for the synthesis of the β-carboline alkaloid. Tetrahedron 2024 155 133903 10.1016/j.tet.2024.133903
    [Google Scholar]
  25. Gaikwad M. Gaikwad S. Kamble R. Synthesis of novel series of 1-(6-hydroxy-4-(1H-indol-3-yl)-3, 6-dimethyl-4, 5, 6, 7-tetrahydro-1H-indazol-5-yl) ethan-1-oneas evaluations of their antimicrobial activity with in silico docking study. J. Med. Chem. Sci. 2022 5 239 248
    [Google Scholar]
  26. Gaikwad S. Kamble D. Lokhande P. Iodine-catalyzed chemoselective dehydrogenation and aromatization of tetrahydro-β-carbolines: a short synthesis of kumujian-c, eudistomin-u, norharmane, harmane harmalan and isoeudistomine-M. Tetrahedron Lett. 2018 59 25 2387 2392 10.1016/j.tetlet.2018.04.043
    [Google Scholar]
/content/journals/cocat/10.2174/0122133372361592250709095118
Loading
Design, Synthesis, In Vitro and In Silico Biological Evaluation of Novel Benzimidazole Derivatives as Antibacterial and Antifungal Agents
Bentham Science Publishers ; https://doi.org/10.2174/0122133372361592250709095118
/content/journals/cocat/10.2174/0122133372361592250709095118
/content/journals/cocat/10.2174/0122133372361592250709095118
Loading

Data & Media loading...

Supplements

Full experimental detail, IR, 1H NMR, Mass spectra and elemental analysis data have been provided in supplementary information.

file format download Download

  • Article Type:     Research Article
Keywords: albendazole ; molecular docking ; Benzimidazole ; molecular dynamics ; antimicrobial ; heterocycle

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test